Targeting NF-κB Signaling in Cancer Stem Cells: A Narrative Review

Among the cell populations existing within a tumor, cancer stem cells are responsible for metastasis formation and chemotherapeutic resistance. In the present review, we focus on the transcription factor NF-kappa B, which is present in every cell type including cancer stem cells. NF-kappa B is involved in pro-tumor inflammation by its target gene interleukin 1 (IL1) and can be activated by a feed-forward loop in an IL1-dependent manner. Here, we summarize current strategies targeting NF-kappa B by chemicals and biologicals within an integrated cancer therapy. Specifically, we start with a tyrosine kinase inhibitor targeting epidermal growth factor (EGF)-receptor-mediated phosphorylation. Furthermore, we summarize current strategies of multiple myeloma treatment involving lenalidomide, bortezomib, and dexamethasone as potential NF-kappa B inhibitors. Finally, we discuss programmed death-ligand 1 (PD-L1) as an NF-kappa B target gene and its role in checkpoint therapy. We conclude, that NF-kappa B inhibition by specific inhibitors of I kappa B kinase was of no clinical use but inhibition of upstream and downstream targets with drugs or biologicals might be a fruitful way to treat cancer stem cells.